This Small Business Innovation Research Phase I project will develop and demonstrate a broad-application prototype Artificial Accessory Cell that can be used as a supplement and/or replacement for cytokines for the directed differentiation of stem cells into desired lineages. While the technology is applicable to all types of stem cells for which some information on its biological niche is available, the initial technology demonstration and suite of products will be focused on hematopoietic stem cells (HSCs) because of the extensive knowledge and range of cytokines available for this well-studied system. Immobilization of biologically active factors is essential to achieving the goal of efficiently directing stem cells along desired pathways for therapeutic aims. In vivo, many important cytokines are presented in membrane-bound, or extra-cellular matrix (ECM)- bound forms[1]. Presentation in this format often induces a unique biological response on the effectors cell that cannot be duplicated using soluble forms of the molecule. In addition, this strategy may be effective for limiting the quantity of expensive signaling molecules necessary for large-scale production of differentiated cells, such as the production of red blood cells for transfusion in an ex vivo format. While other investigators have developed much alternative chemistry for the covalent binding of cytokines to various types of substrates, the focus of this project is to develop and validate a stable, consistent, and commercializable microsphere-based system that can be applied as easily as soluble cytokines. PUBLIC HEALTH RELEVANCE: This Small Business Innovation Research Phase I project will develop and demonstrate the use of Artificial Accessory Cells (AACs) to help guide and control the differentiation of stem cells for therapeutic applications. In order to effectively scale-up and reduce the costs of bringing stem cell therapies to the clinic, more efficient means of providing the growth factors needed to guide stem cells are needed. Use of the proposed AACs has the potential to increase the efficacy and stability of these factors while reducing the costs for large-scale stem cell differentiation.